A novel thiazolidinediones ATZD2 rescues memory deficits in a rat model of type 2 diabetes through antioxidant and antiinflammation

نویسندگان

  • Xuan-Kang Wang
  • Ting Sun
  • Yu-Jiao Li
  • Yu-Hong Wang
  • Yan-Jiao Li
  • Liu-Di Yang
  • Dan Feng
  • Ming-Gao Zhao
  • Yu-Mei Wu
چکیده

Type 2 diabetes (T2DM) has been associated with learning and memory impairment; however, drugs for diabetes could not prevent the development of cognitive decline in T2DM patients. In the present study, compounds derived from thiazolidinediones (TZD), a PPAR-γ agonist, were synthesized by conjuncting the alkyl-substituted benzimidazole group to TZD group (ATZDs). Based on the in vitro evaluation, the neuroprotection of ATZD2 was further investigated using a streptozotocin-induced T2DM rat model. Pharmacokinetic study showed that ATZD2 could pass the blood-brain barrier (BBB) while the rosiglitazone (RSG, the precursor compound of ATZD2) not. Administration of ATZD2 significantly promoted the survival rate and attenuated fasting blood glucose (FBG) levels as compared to RSG treatment in T2DM rats. Furthermore, ATZD2 treatment ameliorated the impairment of learning and memory by Morris water maze test. The beneficial effects of ATZD2 were associated with the down-regulation of hypoxia induced factor-1α, aldose reductase, and Bax expression which are related to T2DM pathology. ATZD2 treatment also attenuated the expression of inflammatory cytokines and restored the balance of redox in the diabetic hippocampus. These effects were more potent as compared with that of RSG at the same dose. The data indicate that ATZD2 may be a potent agent for the treatment of cognitive dysfunction in T2DM.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Sulfur dioxide reduces hippocampal cells death and improves learning and memory deficits in rat model of transient global ischemia/reperfusion

Objective(s): According to recent the findings, sulfur dioxide (SO2) is produced by the cardiovascular system, influencing some major biological processes. Based on previous research, SO2 exhibits antioxidant effects and inhibits apoptosis following cardiac ischemia/reperfusion. Therefore, the objective of the current study was to examine the neuroprotective impact of SO2 following global cereb...

متن کامل

Effect of Sumac Nano-phytosome on Memory and Oxidative Stress in Valproic Acid-induced Rat Model of Autism Spectrum Disorder

Background: Autism Spectrum Disorder (ASD) is an advanced neurological disorder characterized by symptoms such as deficits in social interaction, communication, and cognition. Although sumac fruit contains compounds with antioxidant and anti-inflammatory properties, its effectiveness is limited due to its low bioavailability.  Objective: This study aims to investigate the neuroprotective effec...

متن کامل

Effect of Rheum Ribes Hydro-Alcoholic Extract on Memory Impairments in Rat Model of Alzheimer᾽s Disease

Some animal models have been used to study Alzheimer's disease (AD). AD is an irreversible progressive neurodegenerative disease and the most common cause of dementia. Animal studies have shown that there is a relation between decrease in cholinergic functions in the nucleus basalis of Meynert (NBM) and loss of learning capability and memory. The aim of this study was to investigate the effect ...

متن کامل

Effect of Rheum Ribes Hydro-Alcoholic Extract on Memory Impairments in Rat Model of Alzheimer᾽s Disease

Some animal models have been used to study Alzheimer's disease (AD). AD is an irreversible progressive neurodegenerative disease and the most common cause of dementia. Animal studies have shown that there is a relation between decrease in cholinergic functions in the nucleus basalis of Meynert (NBM) and loss of learning capability and memory. The aim of this study was to investigate the effect ...

متن کامل

Metformin ameliorates learning and memory deficits in streptozotocin-induced diabetic rats

Background and Objective: Diabetes mellitus (DM) in long-term is associated with learning and memory decline. Metformin is an anti-diabetic drug with antioxidant and memory-improving effects. Thus, this research study was conducted to assess the effect of metformin on learning and memory in diabetic rats. Materials and Methods: In the present study, male Wistar rats (n=32) were randomly assign...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2017